Number of Retrieval Attempts Rather Than Procedure Time Is Associated With Risk of Symptomatic Intracranial Hemorrhage.

Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. A direct association between the number of device passes and the occurrence of symptomatic intracranial hemorrhage (SICH) has been suggested. This study represents an in-depth investigation of the hypothesis that >3 retrieval attempts is associated with an increased rate of SICH in a large multicenter patient cohort. Two thousand six hundred eleven patients from the prospective German Stroke Registry were analyzed. Patients who received Endovascular therapy for acute large-vessel occlusion of the anterior circulation with known admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction, and number of retrieval passes were included. The primary outcome was defined as SICH. The secondary outcome was any type of radiologically confirmed intracranial hemorrhage within the first 24 hours. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers, as well as for confounders. Five hundred ninety-three patients fulfilled the inclusion criteria. The median number of retrieval passes was 2 [interquartile range, 1­3]. SICH occurred in 26 cases (4.4%), whereas intracranial hemorrhage was identified by neuroimaging in 85 (14.3%) cases. More than 3 retrieval passes was the strongest predictor for SICH (odds ratio, 3.61 [95% CI, 1.38­9.42], P=0.0089) following adjustment for age, admission National Institutes of Health Stroke Scale, admission Alberta Stroke Program Early CT Score, and Thrombolysis in Cerebral Infarction, as well as time from symptom onset to flow restoration. Baseline Alberta Stroke Program Early CT Score of 8 to 9 (odds ratio, 0.26 [95% CI, 0.07­0.89], P=0.032) or 10 (odds ratio, 0.21 [95% CI, 0.06­0.78], P=0.020) were significant protective factors against the occurrence of SICH. More than 3 retrieval attempts is associated with a significant increase in SICH risk, regardless of patient age, baseline National Institutes of Health Stroke Scale, or procedure time. This should be considered when deciding whether to continue a procedure, especially in patients with large baseline infarctions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect.

BACKGROUND AND PURPOSE: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. METHODS: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0-2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. RESULTS: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0-10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7-7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8-5.6]). CONCLUSIONS: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Lesion Age Imaging in Acute Stroke: Water Uptake in CT Versus DWI-FLAIR Mismatch.

PURPOSE: In acute ischemic stroke with unknown time of onset, magnetic resonance (MR)-based diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) estimates lesion age to guide intravenous thrombolysis. Computed tomography (CT)-based quantitative net water uptake (NWU) may be a potential alternative. The purpose of this study was to directly compare CT-based NWU to magnetic resonance imaging (MRI) at identifying patients with lesion age < 4.5 hours from symptom onset. METHODS: Fifty patients with acute anterior circulation stroke were analyzed with both imaging modalities at admission between 0.5 and 8.0 hours after known symptom onset. DWI-FLAIR lesion mismatch was rated and NWU was measured in admission CT. An established NWU threshold (11.5%) was used to classify patients within and beyond 4.5 hours. Multiparametric MRI signal was compared with NWU using logistic regression analyses. The empirical distribution of NWU was analyzed in a consecutive cohort of patients with wake-up stroke. RESULTS: The median time between CT and MRI was 35 minutes (interquartile range [IQR] = 24-50). The accuracy of DWI-FLAIR mismatch was 68.8% (95% confidence interval [CI] = 53.7-81.3%) with a sensitivity of 58% and specificity of 82%. The accuracy of NWU threshold was 86.0% (95% CI = 73.3-94.2%) with a sensitivity of 91% and specificity of 78%. The area under the curve (AUC) of multiparametric MRI signal to classify lesion age <4.5 hours was 0.86 (95% CI = 0.64-0.97), and the AUC of quantitative NWU was 0.91 (95% CI = 0.78-0.98). Among 87 patients with wake-up stroke, 46 patients (53%) showed low NWU (< 11.5%). CONCLUSION: The predictive power of CT-based lesion water imaging to identify patients within the time window of thrombolysis was comparable to multiparametric DWI-FLAIR MRI. A significant proportion of patients with wake-up stroke exhibit low NWU and may therefore be potentially suitable for thrombolysis. ANN NEUROL 2020;88:1144-1152.

Distinct intra-arterial clot localization affects tissue-level collaterals and venous outflow profiles.

BACKGROUND AND PURPOSE: Arterial clot localization affects collateral flow to ischemic brain in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We determined the association between vessel occlusion locations, tissue-level collaterals (TLC), and venous outflow (VO) profiles and their impact on good functional outcomes. METHODS: We conducted a multicenter retrospective cohort study of consecutive AIS-LVO patients who underwent thrombectomy triage. Baseline computed tomographic angiography (CTA) was used to localize vessel occlusion, which was dichotomized into proximal vessel occlusion (PVO; internal carotid artery and proximal first segment of the middle cerebral artery [M1]) and distal vessel occlusion (DVO; distal M1 and M2), and to assess collateral scores. TLC were assessed on computed tomographic perfusion data using the hypoperfusion intensity ratio. VO was determined on baseline CTA by the cortical vein opacification score. Primary outcomes were favorable VO and TLC; secondary outcome was the modified Rankin Scale after 90 days. RESULTS: A total of 649 patients met inclusion criteria. Of these, 376 patients (58%) had a PVO and 273 patients (42%) had a DVO. Multivariate ordinal logistic regression showed that DVO predicted favorable TLC (odds ratio [OR] = 1.77, 95% confidence interval [CI] = 1.24-2.52, p = 0.002) and favorable VO (OR = 7.2, 95% CI = 5.2-11.9, p < 0.001). DVO (OR = 3.4, 95% CI = 2.1-5.6, p < 0.001), favorable VO (OR = 6.4, 95% CI = 3.8-10.6, p < 0.001), and favorable TLC (OR = 3.2, 95% CI = 2-5.3, p < 0.001), but not CTA collaterals (OR = 1.07, 95% CI = 0.60-1.91, p = 0.813), were predictors of good functional outcome. CONCLUSIONS: DVO in AIS-LVO patients correlates with favorable TLC and VO profiles, which are associated with good functional outcome.

Early clinical surrogates for outcome prediction after stroke thrombectomy in daily clinical practice.

BACKGROUND AND PURPOSE: To investigate early clinical surrogates for long-term independency of patients treated with thrombectomy for large vessel occlusion stroke in daily clinical routine. METHODS: All patients with anterior circulation stroke enrolled in the German Stroke Registry-Endovascular Treatment from 07/2015 to 04/2018 were analysed. National Institute of Health Stroke Scale (NIHSS) on admission, NIHSS percentage change, NIHSS delta and NIHSS at 24 hours as well as existing binary definitions of early neurological improvement (ENI; improvement of 8 (major ENI)/10 (dramatic ENI) NIHSS points or reaching 0/1 were compared for predicting functional outcome at 90 days using the modified Rankin Scale (mRS). Excellent and favourable outcome were defined as 0-1 and 0-2, respectively. RESULTS: Among 2262 endovasculary treated patients with acute ischaemic anterior circulation stroke, NIHSS at 24 hours had the highest discriminative ability to predict excellent (receiver operator characteristics (ROC)NIHSS 24 hours area under the curve (AUC) 0.86 (0.84-0.88)) and favourable long-term functional outcome (ROCNIHSS 24 hours AUC 0.86 (0.85-0.88)) in comparison to NIHSS percentage change (ROC% change AUC mRS ≤1: 0.81 (0.78-0.83) mRS ≤2: 0.81 (0.79-0.83)), NIHSS delta change (ROCΔ change AUC mRS ≤1: 0.74 (0.72-0.77), mRS ≤2: 0.77 (0.74-0.79)) and NIHSS admission (ROCAdm AUC mRS ≤1: 0.70 (0.68-0.73), mRS ≤2: 0.67 (0.68-0.71)). Advanced age was the only independent predictor (adjusted OR 1.05, 95% CI 1.03 to 1.07, p<0.001) for turning the outcome prognosis from favourable (mRS ≤2) to poor (mRS ≥4) at 90 days. CONCLUSION: The NIHSS at 24 hours postintervention with a threshold of ≤8 points serves best as a surrogate for long-term functional outcome after thrombectomy for anterior circulation stroke in daily clinical practice. Only advanced age significantly decreases its predictive value.

Stroke patients treated by thrombectomy in real life differ from cohorts of the clinical trials: a prospective observational study.

BACKGROUND: Randomized controlled trials (RCTs) demonstrated efficacy and safety of endovascular treatment (ET) in anterior circulation large vessel occlusions (LVO). We aimed at investigating how stroke patients treated by thrombectomy in clinical practice and their outcome compare to cohorts and results of thrombectomy trials. METHODS: In a prospective study, we consecutively included stroke patients treated by thrombectomy (2015-2017). Baseline characteristics, procedural and outcome data were analyzed. Outcome was assessed by modified Rankin Scale (mRS) at 90 days. Ordinal regression analysis was performed to identify predictors of outcome. RESULTS: Thrombectomy was applied in 264 patients (median 75 years, 49.6% female). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16, 58.0% received concomitant intravenous thrombolysis, 62.1% were referred from external hospitals. Median Alberta Stroke Program Early CT Score (ASPECTS) was 7. Successful recanalization (modified Thrombolysis in Cerebral Infarction Score, mTICI 2b/3) was achieved in 72.0%. Symptomatic intracranial hemorrhage (sICH) occurred in 4.5%. Independent outcome (mRS 0-2) was achieved in 26.2%, poor outcome (mRS 5-6) in 49.2%. Only 33.5% met the stringent enrolment criteria of previous RCTs. Lower age, baseline NIHSS, pre-stroke mRS, higher ASPECTS, and successful recanalization were independent predictors of favourable outcome. CONCLUSIONS: The majority of stroke patients treated by ET in clinical practice would not have qualified for randomization in prior RCTs. Outcome in real-life patient cohorts is worse than in the highly selected cohorts from randomized trials, while rates of successful recanalization, sICH and outcome predictors are the same. Our findings support ET in broader patient populations than in the RCTs and may improve treatment decision in individual stroke patients with LVO in clinical practice.

Clinical benefit of thrombectomy in stroke patients with low ASPECTS is mediated by oedema reduction.

The impact of endovascular vessel recanalization on patients with a low initial Alberta Stroke Program Early Computer Tomography Score (ASPECTS) is still uncertain. We hypothesized that vessel recanalization leads to an improvement in mortality and degree of disability by reducing brain oedema and malignant mass effect. In this multicentre observational study, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and an ASPECTS of ≤ 5 were analysed. Patients were assembled into two groups: successful vessel recanalization (thrombolysis in cerebral infarctions, TICI scale 2b/3) or persistent vessel occlusion (no endovascular procedure or TICI scale 0-2a). Observers were blinded to clinical data. Net water uptake within brain infarct, a quantitative biomarker based on CT densitometry, was used to quantify oedema in admission and follow-up CT and Δ-water uptake was calculated as difference between water uptake at both time points. Occurrence of malignant infarctions and secondary parenchymal haemorrhage was documented. Furthermore, modified Rankin scale score at 90 days was used for functional outcome. We included 117 patients admitted between March 2015 and August 2017 in three German stroke centres: 71 with persistent vessel occlusion and 46 with successful recanalization. The mean water uptake in the admission imaging was not different between both groups: 10.0% (±4.8) in patients with persistent vessel occlusion and 9.0% (±4.8) in patients with vessel recanalization (P = 0.4). After follow-up CT, the mean Δ-water uptake was 16.0% (±7.5) in patients with persistent vessel occlusion and 8.0% (±5.7) in patients with vessel recanalization (P < 0.001). Successful reperfusion was independently associated with a lowered Δ-water uptake of 8.0% (95% confidence interval, CI: -10.5 to -5.3%; P < 0.001) and lowered modifed Rankin scale score after 90 days of 1.5 (95% CI: -2.2 to -0.8; P < 0.001). The prevalence of malignant infarctions was 44.3% in patients with persistent vessel occlusion and 26.1% in patients with vessel recanalization. There was no significant difference for secondary haemorrhage in both groups (P = 0.7). In conclusion, successful recanalization in patients with low initial ASPECTS resulted in a significant reduction of oedema formation and was associated with a decreased prevalence of malignant infarctions and an improvement of clinical outcome.

Highest Lesion Growth Rates in Patients With Hyperacute Stroke: When Time Is Brain Particularly Matters.

Background and Purpose- The early growth of ischemic lesions has been described as being nonlinear, with lesion growth rates at their highest during the earliest period after stroke onset. We hypothesized that the time gap from imaging to revascularization results in higher lesion growth in patients with hyperacute presentation. Methods- Fifty-one patients with ischemic stroke with initial multimodal computed tomography (CT), follow-up CT after 24 hours, and successful endovascular recanalization were included and separated into 2 groups according to their median time from symptom onset to imaging (eg, hyperacute versus acute). The difference in Alberta Stroke Program Early CT Score (ASPECTS) between initial CT and follow-up CT was assessed, as well as volumetric lesion growth from early ischemic core in admission perfusion CT and total lesion volume in follow-up CT. Results- The median time from onset to imaging was 1.85 hours. There was no significant difference in admission ASPECTS (mean, 8.5 versus 8.2) or time from imaging to recanalization in both groups (median, 2.7 versus 2.4 hours; P=0.4). The mean (SD) lesion growth assessed by ASPECTS difference was 2.7 (2.3) in the hyperacute group and 1.6 (1.3) in the acute group (P=0.03). The mean (SD) volumetric difference in the hyperacute group was 26.6 mL (43.2 mL) and 17.2 mL (26.3 mL; P=0.36) in the acute group, respectively. For every passing hour after onset, ASPECTS lesion growth was reduced by 0.4. Conclusions- Patients in the hyperacute phase showed increased ASPECTS lesion growth from imaging to recanalization suggesting a particular benefit of faster recanalization times in this group of patients with stroke.

Spectrally fat-suppressed coronal 2D TSE sequences may be more sensitive than 2D STIR for the detection of hyperintense optic nerve lesions.

OBJECTIVES: The aim of the study is to compare coronal spectrally fat-suppressed 2D turbo spin-echo (TSE) with 2D short-tau inversion-recovery (STIR) sequences for the detection of optic nerve hyperintensities in patients with acute optic nerve neuritis (ON). METHODS: A retrospective review of patients with suspected unilateral ON and pathological visual evoked potentials, who received coronal TSE and STIR sequences with similar fast and clinically feasible acquisition times in addition to our standard imaging protocol. All images were evaluated and compared concerning the presence of optic nerve lesions, lesion lengths, and signal intensities in different anatomical parts of the optic nerves and CNR measures. A summary confidence score (CS) was calculated based on each reader's subjective confidence regarding the scoring items. RESULTS: Interobserver agreements regarding the detection of optic nerve lesions were excellent for both sequences (TSE, κ = 0.89 and STIR, κ = 0.80). Greater extensions (17.4 ± 6.3 mm vs. 14.1 ± 5.8 mm), as well as higher numbers of optic nerve lesions in symptomatic nerves, were detected on TSE (49/52) compared with STIR (45/52) sequences (both p < 0.001). Overall CS were significantly (p < 0.001) higher for TSE (2.8) compared with STIR (2.1) sequences regarding the presence or absence of optic nerve lesions. CNR ratios of lesions' mean signal intensities vs. ipsilateral surrounding orbital fat and vs. signal intensity measurements from contralateral optic nerves were significantly higher on TSE compared with STIR (p < 0.001 for both comparisons). CONCLUSION: Spectrally fat-suppressed coronal 2D TSE sequences appear to be more sensitive for the detection of hyperintense optic lesions compared with 2D STIR sequences. KEY POINTS: • Spectrally fat-suppressed TSE sequences showed higher detection rates of hyperintense optic nerve lesions, as well as a higher reader confidence scores compared with STIR. • Optic nerve signal abnormalities on TSE sequences were brighter and showed a greater expansion along the optic nerve course. • CNR measures were significantly higher on TSE compared with STIR, when comparing the ratios of mean signal intensities of optic nerve lesions to ipsilateral orbital fat and to contralateral healthy optic nerves of both sequences.

Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction.

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

Recanalization Rate per Retrieval Attempt in Mechanical Thrombectomy for Acute Ischemic Stroke.

Background and Purpose- In acute ischemic stroke, mechanical thrombectomy allows flow restoration in the majority of cases. In case of an unsuccessful retrieval, little is known about how many retrieval attempts should be performed before stopping the procedure. This study assessed the recanalization rate and clinical outcome per retrieval maneuver. Methods- In this analysis, 330 patients with acute large vessel occlusion treated exclusively with stentrieval devices were included. Successful recanalization was defined as Thrombolysis in Cerebral Infarction 2b-3, a good clinical outcome was defined as modified Rankin Scale at 90 days of ≤2. Results- The median number of retrieval attempts was 1 (interquartile range, 1-2, maximum 8). Recanalization rates per retrieval attempt were highest for the first retrieval (46.8%) and lowest for the fifth retrieval (22.7%). After 3 retrieval attempts, 67.9% of patients were successfully recanalized. Patients with 1 to 3 retrieval attempts had higher rates of good clinical outcome (28.9% versus 7.4%; P=0.018). The number of passes was an independent negative predictor of good clinical outcome (adjusted odds ratio, 0.65; 95% CI, 0.435-0.970; P=0.035). Conclusions- Two-thirds of occlusions were successfully recanalized with up to 3 retrieval attempts. Further attempts had good recanalization rates, but the rate of favorable clinical outcome did not improve.

SRC is a signaling mediator in FLT3-ITD- but not in FLT3-TKD-positive AML.

Mutations of Fms-like tyrosine kinase 3 (FLT3) are among the most frequently detected molecular abnormalities in AML patients. Internal tandem duplications (ITDs) are found in approximately 25% and point mutations within the second tyrosine kinase domain (TKD) in approximately 7% of AML patients. Patients carrying the FLT3-ITD but not the FLT3-TKD mutation have a significantly worse prognosis. Therefore, both FLT3 mutations seem to exert different biologic functions. FLT3-ITD but not FLT3-TKD has been shown to induce robust activation of the STAT5 signaling pathway. In the present study, we investigated the mechanisms leading to differential STAT5 activation and show that FLT3-ITD but not FLT3-TKD uses SRC to activate STAT5. Coimmunoprecipitation and pull-down experiments revealed an exclusive interaction between SRC but not other Src family kinases and FLT3-ITD, which is mediated by the SRC SH2 domain. We identified tyrosines 589 and 591 of FLT3-ITD to be essential for SRC binding and subsequent STAT5 activation. Using site-specific Abs, we found that both residues were significantly more strongly phosphorylated in FLT3-ITD compared with FLT3-TKD. SRC inhibition and knock-down blocked STAT5 activation and proliferation induced by FLT3-ITD but not by FLT3-TKD. We conclude that SRC might be a therapeutic target in FLT3-ITD(+) AML.

An RNAi-based system for loss-of-function analysis identifies Raf1 as a crucial mediator of BCR-ABL-driven leukemogenesis.

Genetic loss-of-function studies in murine tumor models have been essential in the analysis of downstream mediators of oncogenic transformation. Unfortunately, these studies are frequently limited by the availability of genetically modified mouse strains. Here we describe a versatile method allowing the efficient expression of an oncogene and simultaneous knockdown of targets of interest (TOI) from a single retroviral vector. Both oncogene and TOI-specific miR30-based shRNA are under the control of the strong viral long terminal repeat promoter, resulting in a single shared RNA transcript. Using this vector in a murine syngeneic BM transplantation model for BCR-ABL-induced chronic myeloid leukemia, we find that oncogene expression and target knockdown in primary hematopoietic cells with this vector is efficient both in vitro and in vivo, and demonstrate that Raf1, but not BRAF, modulates BCR-ABL-dependent ERK activation and transformation of hematopoietic cells. This expression system could facilitate genetic loss-of-function studies and allow the rapid validation of potential drug targets in a broad range of oncogene-driven murine tumor models.

Vessel diameter and catheter-to-vessel ratio affect the success rate of clot aspiration.

BACKGROUND: A direct aspiration first pass technique (ADAPT) is an efficient, safe, cost-effective, and fast thrombectomy technique. OBJECTIVE: To evaluate anatomical and clot characteristics associated with success of the aspiration component as part of ADAPT. METHODS: 106 cases of acute carotid-T, basilar, and middle cerebral artery occlusion undergoing endovascular treatment with ADAPT were retrospectively assessed for successful catheter-clot contact and successful primary aspiration, defined as a Thrombolysis in Cerebral Infarction score ≥2b after primary aspiration with 5F or 6F aspiration catheters. Patient age, National Institutes of Health Stroke Scale (NIHSS) score, time from symptom onset to groin puncture, time from groin puncture to revascularization, aortic arch type, access vessel tortuosity, vessel diameter at the proximal end of the thrombus, catheter-to-vessel ratio (CVR), clot density, length, and perviousness were determined. RESULTS: Successful clot contact with the aspiration catheter was achieved in 76 cases (72%); these patients were younger (67.7±15.2 vs 73.7±11.4 years; p=0.05) and had less tortuous access vessels (1 vs 2 reverse curves; p=0.004) than those in whom clot contact failed. Successful primary aspiration occurred in 36 of these cases (47%) and was associated with significantly smaller vessel diameter at the proximal thrombus end (2.5±0.7 mm vs 3.1±1.3 mm; p=0.01) and higher CVR (CVR outer diameter: 0.85±0.2 vs 0.68±0.2; p=0.01 and CVR inner diameter: 0.72±0.2 vs 0.58±0.2; p<0.001). No significant differences were seen in aortic arch type, radiographic clot features, and NIHSS score. CONCLUSION: With ADAPT, patient age and vessel tortuosity affect the ability to deliver the aspiration catheter and achieve clot contact, whereas vessel diameter and CVR at the aspiration site seem to affect the effectiveness of clot aspiration. Strategies aimed at improving catheter deliverability and increasing CVR may increase the efficacy of ADAPT.

Elevated early lesion water uptake in acute stroke predicts poor outcome despite successful recanalization - When "tissue clock" and "time clock" are desynchronized.

BACKGROUND: Ischemic water uptake in acute stroke is a reliable indicator of lesion age. Nevertheless, inter-individually varying edema progression has been observed and elevated water uptake has recently been described as predictor of malignant infarction. AIMS: We hypothesized that early-elevated lesion water uptake indicates accelerated "tissue clock" desynchronized with "time clock" and therefore predicts poor clinical outcome despite successful recanalization. METHODS: Acute middle cerebral artery stroke patients with multimodal admission-CT who received successful thrombectomy (TICI 2b/3) were analyzed. Net water uptake (NWU), a quantitative imaging biomarker of ischemic edema, was determined in admission-CT and tested as predictor of clinical outcome using modified Rankin Scale (mRS) after 90 days. A binary outcome was defined for mRS 0-4 and mRS 5-6. RESULTS: Seventy-two patients were included. The mean NWU (SD) in patients with mRS 0-4 was lower compared to patients with mRS 5-6 (5.0% vs. 12.1%; p < 0.001) with similar time from symptom onset to imaging (2.6 h vs. 2.4 h; p = 0.7). Based on receiver operating curve analysis, NWU above 10% identified patients with very poor outcome with high discriminative power (AUC 0.85), followed by Alberta Stroke Program Early CT Score (ASPECTS) (AUC: 0.72) and National Institutes of Health Stroke Scale (NIHSS) (AUC: 0.72). CONCLUSIONS: Quantitative NWU may serve as an indicator of "tissue clock" and pronounced early brain edema with elevated NWU might suggest a desynchronized "tissue clock" with real "time clock" and therefore predict futile recanalization with poor clinical outcome.

Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients.

BACKGROUND: In patients suffering from acute ischemic stroke from large vessel occlusion (LVO), mechanical thrombectomy (MT) often leads to successful reperfusion. Only approximately half of these patients have a favorable clinical outcome. Our aim was to determine the prognostic factors associated with poor clinical outcome following complete reperfusion. METHODS: Patients treated with MT for LVO from a prospective single-center stroke registry between July 2015 and April 2019 were screened. Complete reperfusion was defined as Thrombolysis in Cerebral Infarction (TICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as 'poor outcome'. A logistic regression analysis was performed with poor outcome as a dependent variable, and baseline clinical data, comorbidities, stroke severity, collateral status, and treatment information as independent variables. RESULTS: 123 patients with complete reperfusion (TICI 3) were included in this study. Poor clinical outcome was observed in 67 (54.5%) of these patients. Multivariable logistic regression analysis identified greater age (adjusted OR 1.10, 95% CI 1.04 to 1.17; p=0.001), higher admission National Institutes of Health Stroke Scale (NIHSS) (OR 1.14, 95% CI 1.02 to 1.28; p=0.024), and lower Alberta Stroke Program Early CT Score (ASPECTS) (OR 0.6, 95% CI 0.4 to 0.84; p=0.007) as independent predictors of poor outcome. Poor outcome was independent of collateral score. CONCLUSION: Poor clinical outcome is observed in a large proportion of acute ischemic stroke patients treated with MT, despite complete reperfusion. In this study, futile recanalization was shown to occur independently of collateral status, but was associated with increasing age and stroke severity.

Study Criteria Applied to Real Life-A Multicenter Analysis of Stroke Patients Undergoing Endovascular Treatment in Clinical Practice.

Background Randomized controlled clinical trials (RCT) have demonstrated the efficacy of endovascular treatment in anterior circulation large vessel occlusions. However, outcome of patients treated in daily practice differs from the results of the clinical trials. We hypothesize that this is attributable to the study criteria and that application of the criteria on patients undergoing endovascular therapy in daily routine would improve their outcome. Methods and Results Data from a multicenter prospective registry of GSR-ET (German Stroke Registry - Endovascular Treatment) was used. Inclusion criteria and selectivity of SWIFT-PRIME (Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment trial), MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands trial), ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times trial), DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo trial) and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial) trials were analyzed. Baseline characteristics, procedural and outcome data of patients from GSR-ET before and after selection were compared with the results of the RCTs. Furthermore, outcome of patients who underwent endovascular treatment despite not fulfilling the RCT criteria was analyzed. A total of 2611 patients were included (median age, 75 years; 49.6% women; median National Institute of Health Stroke Scale, 16). A minority of patients met all inclusion criteria, ranging from 3% (DEFUSE-3 criteria) to 35% (MR CLEAN criteria). Of the patients fulfilling the MR CLEAN criteria, 41% of patients had a good clinical outcome, compared with 34% of patients that did not fulfill MR CLEAN criteria. Conclusions The RCTs represent a selected population with higher rates of good clinical outcome compared with daily practice. The good outcomes of RCTs can be reproduced in clinical routine in patients who fulfill the RCT inclusion criteria. Furthermore, patients who did not meet the criteria of the RCT still had substantial rates of good clinical outcome.

Feasibility and safety of thrombectomy for isolated occlusions of the posterior cerebral artery: a multicenter experience and systematic literature review.

BACKGROUND: Substantial clinical evidence supporting the benefit of mechanical thrombectomy (MT) for distal occlusions within the posterior circulation is still missing. This study aims to investigate the procedural feasibility and safety of MT for isolated occlusions of the posterior cerebral artery. METHODS: We retrospectively reviewed patients from three stroke centers with acute ischemic stroke attributed to isolated posterior cerebral artery occlusion (IPCAOs) who underwent MT between January 2014 and December 2019. Procedural and safety assessment included successful recanalization rates (defined as Thrombolysis in Cerebral Infarction Scale (TICI) ≥2b), number of MT attempts and first-pass effect (TICI 3), intracranial hemorrhage (ICH), mortality, and intervention-related serious adverse events. Treatment effects were evaluated by the rate of early neurological improvement (ENI) and early functional outcome was assessed with the modified Rankin Scale (mRS) at discharge. A systematic literature review was conducted to identify and summarize previous reports on MT for IPCAOs. RESULTS: Forty-three patients with IPCAOs located in the P1 (55.8%, 24/43), P2 (37.2%, 16/43), and P3 segment (7%, 3/43) were analyzed. The overall rate of successful recanalization (TICI ≥2b) was 86% (37/43), including a first pass-effect of 48.8% (21/43) leading to TICI 3. sICH occurred in 7% (3/43) and there were two cases with iatrogenic vessel dissection and one perforation. ENI was observed in 59% (23/39) and excellent functional outcome (mRS ≤1) in 46.2% (18/39) of patients who were discharged. The in-hospital mortality rate was 9.3% (4/43). CONCLUSION: Our study suggests the technical feasibility and safety of thrombectomy for IPCAOs. Further studies are needed to investigate safety and long-term functional outcomes with posterior circulation stroke-adjusted outcome assessment.

Factors Associated with Failure of Reperfusion in Endovascular Therapy for Acute Ischemic Stroke : A Multicenter Analysis.

AIM: In acute large vessel occlusions, endovascular therapy (EVT) achieves flow restoration in the majority of cases; however, EVT fails to achieve sufficient reperfusion in a substantial minority of patients. This study aimed to identify predictors of failed reperfusion. METHODS: In this study 2211 patients from the German Stroke Registry who received EVT for anterior circulation stroke were retrospectively analyzed. Failure of reperfusion was defined as thrombolysis in cerebral infarction (TICI) grades 0/1/2a, and sufficient reperfusion as TICI 2b/3. In 1629 patients with complete datasets, associations between failure of reperfusion and baseline clinical data, comorbidities, location of occlusion, and procedural data were assessed with multiple logistic regression. RESULTS: Failure of reperfusion occurred in 371 patients (16.8%) and was associated with the following locations of occlusion: cervical internal carotid artery (ICA, adjusted odds ratio, OR 2.01, 95% confidence interval, CI 1.08-3.69), intracranial ICA without carotid T occlusion (adjusted OR 1.79, 95% CI 1.05-2.98), and M2 segment (adjusted OR 1.86, 95% CI 1.21-2.84). Failed reperfusion was also associated with cervical ICA stenosis (>70% stenosis, adjusted OR 2.90, 95% CI 1.69-4.97), stroke of other determined etiology by TOAST (Trial of ORG 10172 in acute stroke treatment) criteria (e.g. nonatherosclerotic vasculopathies, adjusted OR 2.73, 95% CI 1.36-5.39), and treatment given outside the usual working hours (adjusted OR 1.41, 95% CI 1.07-1.86). Successful reperfusion was associated with higher Alberta stroke program early CT score (ASPECTS) on initial imaging (adjusted OR 0.85, 95% CI 0.79-0.92), treatment with the patient under general anesthesia (adjusted OR 0.72, 95% CI 0.54-0.96), and concomitant ICA stenting in patients with ICA stenosis (adjusted OR 0.20, 95% CI 0.11-0.38). CONCLUSION: Several factors are associated with failure of reperfusion, most notably occlusions of the proximal ICA and low ASPECTS on admission. Conversely, stent placement in the proximal ICA was associated with reperfusion success.